Alzheimer’s Disease in People With Down Syndrome: Risk, Timing and Screening
People with Down syndrome have a 90% to 95% lifetime risk of Alzheimer’s disease. Amyloid accumulation is almost inevitable by age 40, and baseline assessment is recommended by age 40 with annual follow-up.
Individuals with Down syndrome have a nearly inevitable risk of developing Alzheimer’s disease, with lifetime risk estimates of 90% to 95%. Individuals with Down syndrome carry an additional copy of chromosome 21, the site where the gene for the amyloid precursor protein lies, leading to overproduction and accumulation of amyloid protein in the brain, a fundamental pathological process in Alzheimer’s disease.
By around the age of 35 and certainly by age 40, accumulation of amyloid is almost inevitable. Symptoms often will start five to 10 years later, or maybe a little after that, with onset of symptoms somewhere in the mid-40s to mid-50s.
There is a certain predictability, at least biologically, in the progression of the amyloid deposition. However, just as in sporadic Alzheimer’s disease, there are some individuals who have amyloid present but who seem resilient, at least resilient to developing some of the symptoms or decline seen clinically. There is some heterogeneity in the symptom progression, yet it is a very predictable disease from a biological standpoint.
Alzheimer’s disease may be underrecognized in this population for a number of reasons. Down syndrome patients did not used to have the longevity they do now, but now it is much more likely that an individual with Down syndrome who has control over their other medical issues will make it into their 60s. When individuals already have intellectual developmental disability of various levels, cognitive or functional decline sometimes just gets washed out, and people may not think about a secondary process that might be going on.
There are some general guidelines for screening and monitoring. Probably at least by the age of 40, the person should undergo some baseline assessment of their functional capacity and maybe even their cognitive capacity, and then subsequently some type of annual examination. If there is a change, that should lead to further workup for cognitive impairment, including looking for other comorbidities that could cause the problem, and various tools available for the diagnosis of Alzheimer’s disease can be applied to this population as well.